Ovarian cancer represents a major clinical challenge in gynecologic oncology. Most patients are asymptomatic until the disease has metastasized, two-thirds are diagnosed only at an advanced stage. As a result, ovarian cancer has the highest fatality-to-case ratio of all gynecologic malignancies. In spite of cytoreductive surgery and combination chemotherapy, the 5-year survival rate of patients with advanced ovarian cancer is only 20-30%. [Holschneider, C. H. and Berek J. S., Semin. Surg. Oncol. 19:3-10 (2000)].
Ovarian cancer develops mainly from the malignant transformation of a single cell type, the surface epithelium. Although the biologic mechanism of transformation remains unclear, it is reported to involve a multi-step process requiring an accumulation of genetic lesions that affect several different classes of genes. [Holschneider, supra.].
Oncogenes encode proteins that participate in growth-stimulatory pathways in normal cells. Activation of these genes (as a result of amplification, translocation, or mutation) contributes to the development of epithelial ovarian cancers. [Holschneider, supra.].
One method of treating these epithelial ovarian cancers entails administration with platinum-based chemotherapy drugs or platinates. Platinates are cytotoxic drugs containing a core atom of platinum, including cisplatin, carboplatin and analogs thereof. They are DNA-damaging agents and are used in the treatment of cancer because of their efficacy. Cisplatin (cis-diamminedichloroplatinum) is used particularly in the treatment of solid tumors. It has been reported that aggressive regimens of cisplatin and its analog carboplatin boost the clinical response rates of advanced ovarian cancer to 60-80%, but 30-40% of initial responders subsequently relapse with tumors that resist cisplatin. [Holschneider, supra.]. Thus, the toxicity of these agents and the development of resistance to these agents continues to be problematic.